Survival Outcomes In Patients Research Articles

Survival outcomes in early-onset oesophageal adenocarcinoma patients: A systematic review and meta-analyses

BACKGROUND The incidence of oesophageal adenocarcinoma (OAC) has been reported to be increasing in many countries. Alongside this trend, an increase in incidence of early-onset OAC, defined as OAC in adults aged under 50 years, has been observed. It is unclear whether survival outcomes for early-onset OAC patients differ from older age groups. AIM To investigate survival outcomes in early-onset OAC patients. METHODS Ovid Medline and Embase were searched from inception to January 2022 for relevant studies relating to early-onset OAC and survival outcomes. Results regarding the overall five-year survival and risk of death of younger and older patients with OAC were extracted and pooled using meta-analyses to produce pooled estimates and 95%CIs where possible. RESULTS Eleven studies which compared survival of early-onset OAC, defined as age at diagnosis of < 50 years, with older patients were included. A narrative review of median and mean survival demonstrated conflicting results, with studies showing early-onset OAC patients having both better and worse outcomes compared to older age groups. A meta-analysis of five-year survival demonstrated similar outcomes across age groups, with 22%-25% of patients in the young, middle and older age groups alive after five years. A meta-analysis of four studies demonstrated that early-onset OAC patients did not have a significantly increased risk of death compared to middle-aged patients (hazard ratio 1.12, 95%CI: 0.85-1.47). CONCLUSION Results suggest that early-onset OAC patients do not have a significantly different survival compared to older patients, but further population-based research, taking into account stage and treatment, is required.

Clinical characteristics and survival outcomes of patients with primary central nervous system lymphoma treated with high-dose methotrexate-based polychemotherapy and consolidation therapies

Given the rarity of primary central nervous system lymphoma (PCNSL), evaluations of different high-dose methotrexate-(HD-MTX)-based treatment regimens is sparse. This retrospective, multicenter study evaluates clinical characteristics and outcomes (progression-free, overall and disease-specific survival) after five HD-MTX-based polychemotherapeutic regimens and two consolidation therapies. 346 patients with histologically confirmed PCNSL, treated with ≥ 1 cycle HD-MTX-based strategies (≥3g/m2/cycle) were included. The regimens included MATRIX (HD-MTX, HD-AraC, thiotepa, and rituximab), (R)MBVP±HD-AraC (HD-MTX, teniposide/etoposide, carmustine, prednisolone, ± HD-AraC, ± rituximab), (R)MP (HD-MTX, procarbazine, ± rituximab), and a combination of HD-MTX and HD-AraC. The overall response rate after induction was 69 %, 28 % complete remission and progressive disease was observed in 100 (29 %) patients. 126 (36 %) patients received consolidation, including high-dose-BCNU-thiotepa with autologous stem cell transplantation (HD-BCNU-TT/ASCT, n = 59 (17 %)) or whole brain radiotherapy (WBRT, n = 67 (19 %)). Clinical characteristics associated with adverse mortality risk by multivariable prognostication contained age > 60 years (HR 1.61, p = 0.011), elevated LDH (HR 1.75, p = 0.004) and WHO status ≥ 2 (HR 1.56, p = 0.010). Independently, induction regimens containing HD-AraC demonstrated survival benefit compared to induction regimens without HD-AraC (HR 0.59, p = 0.002). Without preference for HD-BCNU-TT/ASCT or WBRT, a favorable effect of consolidation (HR 0.44 and HR 0.42, p < 0.001) was confirmed, also with consolidation as time-dependent variable. Competing risk analysis showed similar low incidence of lymphoma-unrelated deaths in consolidated and unconsolidated patients. This study confirms that age, elevated LDH and WHO status increase the mortality risk. HD-AraC containing treatment regimens and consolidation with HD-BCU-TT/ASCT or WBRT were associated with superior survival, including a favorable low incidence of lymphoma-unrelated deaths.

Analysis of postoperative complications and long term survival following radical gastrectomy for patients with gastric cancer

This study aimed to analyze the complications and long-term survival outcomes in patients who underwent radical gastrectomy for gastric cancer, as well as to identify the risk factors associated with postoperative complications. After conducting a comprehensive search within the medical records system, a total of 2508 patients who underwent radical gastrectomy and met the inclusion criteria were enrolled. Of the 2508 patients, 301 were diagnosed with postoperative complications. The pathological data, postoperative recovery, and survival outcome were compared between complication and control group. Subsequently, univariate and multivariate logistic regression analyses were conducted to identified the risk factors. According to the Clavien-Dindo grading criteria for postoperative complications, the proportions of grade I, II, III, IV, and V complications following radical gastrectomy were observed to be 28.2%, 42.9%, 19.6%, 8.0%, and 1.3%, respectively. The presence of postoperative complications significantly prolonged the duration of gastrointestinal decompression (P < 0.001), catheter retention (P < 0.001), fasting (P < 0.001), and hospitalization (P < 0.001). Additionally, it had a detrimental impact on survival outcomes. Age > 65years [odds ratio (OR) = 1.378, P = 0.020], presence of diabetes (OR = 2.042, P < 0.001), operative duration > 215 min (OR = 1.450, P = 0.006), intraoperative blood loss > 275 ml (OR = 1.474, P = 0.004), and Roux-en-Y anastomosis for both whole stomach (OR = 1.567, P = 0.021) and distal gastric cancer (OR = 2.083, P = 0.003) were identified as independent risk factors for postoperative complications. This study analyzed the complications and survival outcomes following radical gastrectomy, and investigated the predictors for postoperative complications, thereby providing valuable guidance on the prevention and management of surgical complications in gastric cancer.

Deciphering a hydrogen sulfide-related signature to supervise prognosis and therapeutic response in colon adenocarcinoma.

Hydrogen sulfide (H2S) is a critical molecule that participates in various molecular, physiological, and pathophysiological processes in biological systems. Emerging evidence has revealed that H2S is implicated in the progression of colon cancer and immune escape. Against this backdrop, the present study aimed to construct a prognostic risk feature for colon adenocarcinoma (COAD) by leveraging hydrogen sulfide-related genes (HSRG). Transcriptomic data and corresponding clinical-pathological information of colon cancer were obtained from The Cancer Genome Atlas and gene expression omnibus databases. Univariate Cox regression analysis was employed to assess the prognostic relevance of HSRG. Consensus clustering was utilized to perform molecular subtyping of COAD, followed by comparison of immune cell infiltration, drug sensitivity, and immune therapy response between subtypes. Differential expression gene and gene set enrichment analyses were conducted between subtypes. Univariate, lasso, and multivariate Cox regression analyses were applied to construct a prognostic model derived from HSRG. A nomogram model for predicting COAD prognosis was constructed and evaluated. In this study, we identified 12 HSRGs that were associated with COAD prognosis. Consensus clustering analysis revealed 3 COAD molecular subtypes that exhibited significant differences in terms of prognosis, tumor immune cell infiltration, drug sensitivity, and immune therapy response. Gene set enrichment analysis demonstrated that immunoregulatory processes were significantly suppressed in the poor-prognosis subtype while Wnt-related pathways and processes were significantly upregulated. Based on the differentially expressed genes between subtypes, we constructed a risk model comprising 11 genes that effectively distinguished high-risk patients from low-risk patients with significant associations with patient survival outcomes, drug treatment, pathological staging, and T staging. The HSRG-derived risk feature was an independent prognostic factor for COAD in drug treatment and pathological staging and could be integrated into a nomogram for prognosis prediction. Calibration curve, receiver operating characteristic curve, and decision curve analysis demonstrated excellent performance of the nomogram in evaluating COAD prognosis. Our study systematically assessed the prognostic significance of HSRG in COAD, identified HSRG-based molecular subtypes and risk features, and highlighted their potential utility in predicting prognosis and treatment response.

Development and validation of nomogram for predicting the cancer-specific survival among patients aged 80 and above with early-stage non-small cell lung cancer.

The use of nomograms in predicting the prognosis of early-stage non-small cell lung cancer (NSCLC), particularly in elderly patients, is not widespread. A validated prognostic model specifically for NSCLC patients over 80 years old holds promising potential for clinical application in forecasting patient outcomes. The prognostic value of various factors for NSCLC patients aged 80 and above was evaluated using data from the Surveillance, Epidemiology, and End Results (SEER) database (2010-2017). Kaplan-Meier (KM) curves, Cox proportional hazards regression models, and nomogram were utilized to evaluate the impact of each factor on cancer-specific survival (CSS). A cohort comprising 7045 individuals was selected for inclusion in the analysis. Through rigorous statistical analysis, 10 independent prognostic factors were identified and incorporated into the nomogram. The nomogram's receiver operating characteristic (ROC) curve area under the curve (AUC) was higher than that of the AJCC 7th edition TNM staging system's predicted CSS (0.744 versus 0.602), establishing the superior prognostic value of the nomogram. We have successfully created a highly accurate and discriminative nomogram that enables oncologists to predict the survival outcome of each individual patient with I/II NSCLC who is 80 years or older.

Development of graded prognostic assessment for breast Cancer brain metastasis incorporating extracranial metastatic features: a retrospective analysis of 284 patients

BackgroundBreast cancer brain metastasis (BCBM) is associated with poor survival outcomes and reduced quality of life. The Graded Prognostic Assessment (GPA) score model serves as a well-established tool for predicting the prognosis of BCBM. Notably, the presence of extracranial metastasis (ECM) is considered as a significant prognostic factor in the breast GPA model. This study aims to further refine other features of ECM to enhance the prognostic prediction for BCBM.MethodsThis study included all inpatients diagnosed with BCBM at the Cancer Hospital, Chinese Academy of Medical Sciences, from January 2010 to July 2021. Baseline characteristics of patients were compared based on features of ECM, including the presence, number, location, and control status of metastases. Overall survival (OS) were compared using the Kaplan–Meier method with log-rank tests. Cox regression analyses were conducted to identify significant prognostic factors. The aforementioned ECM features were incorporated into the original Breast-GPA model to enhance its prognostic accuracy. The concordance index (C-index) and restricted mean survival time (RMST) were utilized to evaluate and compare the predictive accuracy of the updated and original survival models.Results284 patients with BCBM were included in the study. Kaplan–Meier survival curves suggested that patients without ECM when diagnosed with BCBM showed better survival (p = 0.007). In the subgroups with ECM, more than 3 organs involved, both bone and visceral metastasis and progressive ECM portended dismal OS (p = 0.003, 0.001 and <0.001). Multivariate analysis demonstrated that molecular subtype, presence of ECM, and number of brain metastasis significantly influenced OS after BCBM. By modifying the current GPA model to include more precise characteristics of ECM, the predictive accuracy was further enhanced as indicated by the C-index and RMST curve.ConclusionsMore ECM sites, both bone and visceral invasion and uncontrolled ECM were dismal prognostic factors for survival outcomes of BCBM patients. A new Breast-GPA model with better predictive effect was constructed.

Survival outcomes of patients with diffuse large B-cell lymphoma undergoing autologous stem cell transplantation in Germany: real-world evidence from an administrative database between 2010 and 2019.

Limited real-world evidence is available for patients with diffuse large B-cell lymphoma (DLBCL) who received an autologous stem cell transplantation (ASCT) in Germany. This study aims to describe the real-world survival outcomes of patients with DLBCL who received ASCT in Germany after diagnosis. This study is a retrospective database analysis covering the period between 2010 and 2019. Unadjusted overall survival (OS) was plotted using the Kaplan-Meier estimator for the overall population and stratified by relapse status. A Cox regression was run to identify factors that influence OS. A total of 112 patients received an ASCT, with the average time from first-line treatment to ASCT being 11.7 months. The median OS estimated by Kaplan-Meier was 83.4 months for the entire cohort. The only variable that significantly reduced the OS was the presence of subsequent treatment after ASCT in a time-dependent model. OS after ASCT for DLBCL patients in Germany is higher than previously reported and may still be considered a valid option for carefully selected patients with relapsed/refractory DLBCL.

Development and validation of a prognostic model for colon cancer based on mitotic gene signatures and immune microenvironment analysis

BackgroundMitotic processes play a pivotal role in tumor progression and immune responses. However, the correlation between mitosis-related genes, clinical outcomes, and the tumor microenvironment (TME) in colon cancer remains unclear. This study aims to develop a prognostic and therapeutic significance model for colon cancer based on mitosis-related genes.MethodsRNA expression profiles and clinical data of 453 colon cancer patients were downloaded from The Cancer Genome Atlas (TCGA). Mitosis-related genes were selected from the MsigDb database. The gene model was constructed using differential analysis, univariate and multivariate Cox regression, and Lasso regression analyses. The predictive model was validated using data from the GSE17536, GSE17537, and GSE39582 datasets. Predictive accuracy was evaluated via Receiver Operating Characteristic (ROC) curves, while nomograms were developed by integrating clinical and pathological features. Gene set enrichment analysis explored biological processes and pathways linked to the model. TME was assessed using ESTIMATE, and the proportion and function of immune cells were analyzed through CIBERSORT. Drug sensitivity analysis was conducted using the CTRP database.ResultsA predictive model based on 17 mitosis-related genes (KIFC1, CCNF, EME1, CDC25C, ORC1, CCNJL, ANKRD53, MEIS2, FZD3, TPD52L1, MAPK3, CDKN2A, EDN3, NPM2, PSRC1, INHBA, BIRC5) was created. The model exhibited robust predictive performance across both training and validation cohorts. Nomograms for predicting 3-, 5-, and 7-year survival rates in colon cancer (COAD) patients were generated. The model's correlation with immune cell infiltration and function was highlighted.ConclusionThe mitosis-related gene model serves as a valuable indicator for predicting survival outcomes in colon cancer patients.

Single cell analysis revealed SFRP2 cancer associated fibroblasts drive tumorigenesis in head and neck squamous cell carcinoma

Understanding the mechanisms of invasion and metastasis in head and neck squamous cell carcinoma (HNSCC) is crucial for effective treatment, particularly in metastatic cases. In this study, we analyzed multicenter bulk sequencing and comprehensive single-cell data from 702,446 cells, leading to the identification of a novel subtype of cancer-associated fibroblasts (CAFs), termed Secreted Frizzled-Related Protein2 CAFs (SFRP2_CAFs). These cells, originating from smooth muscle cells, display unique characteristics resembling both myofibroblastic CAFs and inflammatory CAFs, and are linked to poorer survival outcomes in HNSCC patients. Our findings reveal significant interactions between SFRP2_CAFs and SPP1 tumor-associated macrophages, which facilitate tumor invasion and metastasis. Moreover, our research identifies Nuclear factor I/X (NFIX) as a key transcription factor regulating SFRP2_CAFs behavior, confirmed through gene regulatory network analysis and simulation perturbation.

Clinical Outcomes of Concomitant Coronary Artery Bypass Grafting During Ventricular Septal Myectomy.

The clinical characteristics and survival outcomes of patients who underwent concomitant coronary artery bypass grafting during septal myectomy have not been well studied. We reviewed patients who underwent both septal myectomy and coronary artery bypass grafting from 2009 to 2020. Causes of concomitant grafting and their impact on survival were analyzed. The median follow-up period was 5.1 years. A total of 320 patients underwent both grafting and myectomy. Of these, 69.7% and 28.1% underwent grafting attributed to atherosclerotic coronary artery disease and myocardial bridging, respectively. Patients who underwent grafting for coronary artery disease tended to be older, had a longer bypass time, and required more grafts compared with patients undergoing procedures because of myocardial bridging (all P<0.05). Postoperatively, the left ventricular outflow gradient significantly decreased from 85.4 mm Hg to 12.8 mm Hg (P<0.001) without perioperative death. The cumulative survival rates were 96.2% and 97.6% at 5 years in the coronary artery disease and myocardial bridging groups, respectively, and they were comparable to that of general myectomy cohort (hazard ratio [HR], 1.06 [95% CI, 0.47-2.36], P=0.895 and HR 0.75 [95% CI, 0.23-2.46], P=0.636, respectively). Sudden death accounted for 45.5% (5 of 11) of postoperative mortality. Analysis of composite end point events showed decreased morbidity with at least one arterial graft in the overall cohort (HR, 0.47 [95% CI, 0.23-0.94], P=0.034). Concomitant grafting in septal myectomy was found to be a safe procedure. Patients who underwent such surgery experienced favorable postoperative outcomes comparable to those who underwent septal myectomy alone, with a 5-year survival rate of >95% and improved functional class of >90%.

Effects of Intraoperative Opioid Use and a Combined Anesthesia Protocol in Patients Undergoing Radical Cystectomy for Urothelial Carcinoma of the Bladder—A Single-Center Experience

Background: An increased intraoperative opioid dose seems to lead to worse outcomes in several types of cancer. We assessed the effect of intraoperatively administered opioids as well as the type of anesthesia on survival, recurrence rates and major perioperative outcomes in patients who underwent radical cystectomy (RC) for urothelial carcinoma of the urinary bladder. Methods: We included patients who underwent open RC at our center between 2015 and 2022. The role of the type and dosage of intraoperative opioid agents, such as remifentanil, sufentanil and morphine milligram equivalents (MME), as well as the type of anesthesia (intravenous only versus intravenous/epidural), was assessed regarding perioperative and long-term outcomes after RC. Results: A total of 508 patients with a median age of 73 years (IQR: 64–78) were included. Overall, 92 (18%) patients received intravenous anesthesia, whereas 416 (82%) received combined anesthesia. At a median follow-up of 270 days (IQR: 98–808), 108 (21%) deaths and 106 (21%) recurrences occurred. Combined anesthesia was associated with better survival (HR:0.63, 95% CI: 0.4–0.97, p = 0.037) and lower intensive care unit admission rates (OR: 0.49, 95% CI: 0.31–0.77, p = 0.002) in the univariate analysis (unadjusted). The type and dosage of intraoperative opioid agents did not affect long-term survival and recurrence rates, as well as major perioperative outcomes. Nevertheless, the findings of our study were limited by its single-center, retrospective design. Conclusion: The use of intraoperative opioids was not associated with worse outcomes in our cohort, while the use of additional epidural anesthesia seems to be beneficial in terms of overall survival and intensive care unit admissions. Nevertheless, further research is mandatory to validate the safety of opioids in patients undergoing RC.

Multidimensional analysis of the impact of Gemmatimonas, Rhodothermus, and Sutterella on drug and treatment response in colorectal cancer.

Colorectal cancer is the third most prevalent cancer across the globe. Despite a diversity of treatment methods, the recurrence and mortality rates of the disease remain high. Recent studies have revealed a close association of the gut microbiota with the occurrence, development, treatment response, and prognosis of colorectal cancer. This study aims to integrate transcriptome and microbiome data to identify colorectal cancer subtypes associated with different gut microbiota and evaluate their roles in patient survival prognosis, tumor microenvironment (TME), and drug treatment response. An integrated analysis of microbiome data was conducted on samples of colorectal cancer from public databases. Based on this, two tumor subtypes (C1 and C2) closely associated with patient survival prognosis were identified and a risk score model was constructed. The survival status, clinical parameters, immune scores, and other features were analyzed in-depth, and the sensitivity of various potential drugs was examined. A thorough examination of microbiome information obtained from colorectal cancer patients led to the identification of two primary tumor clusters (C1 and C2), exhibiting notable variations in survival outcomes. Patients with the C1 subtype were closely associated with better prognosis, while those with the C2 subtype had higher gut microbial richness and poorer survival prognosis. A predictive model utilizing the microbiome data was developed to accurately forecast the survival outcome of patients with colorectal cancer. The TME scores provided a biological basis for risk assessment in high-risk (similar to the C2 subtype) patient cohorts. Evaluation of the sensitivity of different subtypes to various potential drugs, indicated the critical importance of personalized treatment. Further analysis showed good potential of the developed risk-scoring model in predicting immune checkpoint functions and treatment response of patients, which may be crucial in guiding the selection of immunotherapy strategies for patients with colorectal cancer. This study, through a comprehensive analysis of colorectal cancer microbiome, immune microenvironment, and drug sensitivity, enhances the current understanding of the multidimensional interactions of colorectal cancer and provides important clinical indications for improving future treatment strategies. The findings offer a new perspective on improving treatment response and long-term prognosis of patients with CRC through the regulation of microbiota or the utilization of biomarkers provided by it.

The prognostic value of skeletal muscle mass and density in breast cancer: a systematic review and meta-analysis.

Aim: The effect of skeletal muscle mass and density on the long-term survival outcome of breast cancer patients is unclear.Materials & methods: Systematically searched all articles in PubMed, Web of science, Springerlink, EMBASEand Wiley databases that studied the association between skeletal muscle and survival outcomes of breast cancer by 25September 2023. The hazard ratios and confidence intervals of the multiple factor analysis results controlling for confounding variables in the study were collected and analyzed using STATA 14.0 software.Results: This meta-analysis included a total of 13 studies, with a median age of 48.2years. Meta results showed that the survival (hazard ratio [HR]: 0.98, 95% CI: 0.89-1.08) and recurrence (HR: 0.96, 95% CI: 0.92-1.00) outcomes of breast cancer patients with sarcopenia were not significantly affected compared with those without sarcopenia. No significant heterogeneity or publication bias was observed in the study.Conclusion: The conclusion that skeletal muscle is regarded as a useful factor that can guide and optimize the prognosis of breast cancer patients is uncertain, or the result is very weak. Considering the impact of research quality and confounding factors, prospective studies are needed in the future to further demonstrate.PROSPERO identifier: CRD42023463480 (www.crd.york.ac.uk/prospero).

Evaluation of prognostic factors for late recurrence in clear cell renal carcinoma: an institutional study.

Following nephrectomy with curative intent, a subset of patients diagnosed with non-metastatic renal cell carcinoma (nmRCC) will present late recurrences, with metastatic relapses after 5 years from the surgical intervention. The aim of this study is to evaluate the prevalence of late recurrences in Romanian patients with nmRCC that have undergone surgery and to assess the clinicopathological characteristics prognostic for late-relapse RCC. This is a single-center, retrospective and observational study that analyzed patients with nmRCC with clear cell histology who underwent surgical resection of the primary tumor with curative intent. The patients included in the study were treated and further surveilled according to a personalized follow-up plan between January 2011 and December 2012 in The Oncology Institute "Prof. Dr. Ion Chiricuţă", Cluj-Napoca, Romania. Study endpoints included median disease-free survival (DFS), median overall survival (OS), as well as evaluation of possible prognostic factors indicative of late relapse. In the study cohort (n=51), the median DFS was 46 months and median OS was 130 months. DFS was significantly correlated with the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score (p=0.04, HR=2.48; 95% CI [1.02, 6.01]), neutrophil to lymphocyte ratio (NLR) (a higher NLR value was associated with a poorer DFS, p=0.035), tumor size (T4 tumors vs. T1 p<0.05, HR=9,81; 95% CI [2.65, 36.27]) and Fuhrman nuclear grade (Fuhrman grade 1 vs. Fuhrman grade 3 p<0.05, HR=4,16; 95% CI = [1.13,15.22]). Fifty one percent of the patients included experienced disease relapse. From this subgroup, a significant percentage of 42% patients presented disease recurrence after 60 months from nephrectomy. OS was correlated to IMDC score (p=0.049, HR=2.36; 95% CI [1, 5.58]) and Fuhrman nuclear grade (Fuhrman grade 1 vs. Fuhrman grade 3 p<0.05, HR=3,97; 95% CI [1.08, 14.54]). The results of this study support the previously presented biological behavior of RCC, demonstrating that late recurrences in RCC are not uncommon occurrences and patients with localized RCC should be followed up for a longer interval after the surgery for the primary tumor. In addition, the study strengthens the data supporting certain biomarkers as valuable prognostic factors determining survival outcomes of patients with RCC.

Quality of life and late therapy effects in pediatric non-Hodgkin lymphoma survivors: Insights from a single-institution study.

The survival outcomes of pediatric patients with mature B-non-Hodgkin lymphoma (NHL) have improved due to advances in treatment. We aimed to assess the frequency and severity of late effects and their impact on quality of life among pediatric NHL survivors. This retrospective study included patients diagnosed with mature B-NHL at Children's Cancer Hospital of Egypt (CCHE) 57357 from January 2012 through December 2015. Patients received treatment according to the modified LMB 96 protocol. The minimum follow-up period was 5years. Assessments for toxicity and quality of life were conducted at regular intervals during and after treatment. Patients were assessed for toxicity including pulmonary dysfunction, cardiac dysfunction, lipid profile abnormalities, endocrine dysfunction (thyroid function, vitamin D levels, growth curves), and cognitive function (intelligence quotient [IQ] level using Stanford-Binet Intelligence Scales-5th Edition, and quality of life (QoL) assessment (PedsQoL). A total of 273 patients were eligible, and 206 were evaluable. Median age was 5.45 (range: 2.4-18), with a male-to-female ratio 4:1. Pulmonary function abnormalities were detected in 119/203 (58.6%); most had mild dysfunction (72/119, 60.5%), while 17% had severe dysfunction. Cardiac toxicity occurred in 10% of the patients (n=20). IQ testing showed that 52 patients had a low average IQ score, while 151 patients had either average or above average scores. The total mean QoL score was 99±0.058 classified as "satisfactory." However, significant impairment of the physical domain of quality of life was observed among group C patients compared to A/B (p=.033), older age at diagnosis (p=.042), and those with pulmonary dysfunction (p<.001). Total score of quality of life was significantly impaired among patients with pulmonary dysfunction (p=.009), likewise older age at diagnosis (p=.017) and those with low average IQ scores (p=.033). Childhood mature B-NHL survivors are at significant risk for late effects; pulmonary dysfunction and low average IQ that can subsequently impact QoL.

Deep Learning Models for Early Detection of Ovarian Cancer: A Systematic Review of Ultrasound-Based Diagnostic Tools

Ovarian Cancer (OC) remains one of the most lethal gynecological malignancies, with a global 5-year survival rate of only 45%. This project aimed to assess the potential of deep learning-based diagnostic tools in improving early detection of ovarian cancer, particularly through ultrasound imaging. The primary research problem lies in the challenge of accurately diagnosing OC at an early stage, as traditional imaging techniques often rely on subjective interpretations, leading to inconsistent results. To address this issue, a systematic review was conducted following PRISMA guidelines, evaluating studies published between January 2018 and May 2023 in the Scopus and PubMed databases. These studies employed deep learning or artificial intelligence models for the diagnosis, prognosis, or identification of OC from ultrasound images. Of the 101 studies screened, 9 met the inclusion criteria. The included studies reported diagnostic accuracies of deep learning models ranging from 75% to 100%, with sensitivities between 85% and 99%. The conclusions indicate that deep learning models significantly enhance the diagnostic accuracy of ovarian cancer, offering a promising non-invasive tool for early detection. This research underscores the importance of integrating AI technologies into clinical practice to improve survival outcomes for OC patients.

7427 Cellular Senescence As A Pro-Tumorigenic Process And Therapeutic Target In Adrenocortical Carcinoma

Abstract Disclosure: L. Smith: None. K. Warde: None. S. Haston: None. J. Martinez-Barbera: None. K. Basham: None. Adrenocortical carcinoma (ACC) is a rare, yet highly aggressive malignancy that arises in the adrenal cortex. Advanced age is a major risk factor for ACC, with the peak age incidence between 50 and 60 years old. Older individuals above age 50 also have significantly worse survival outcomes. A better understanding of how aging contributes to the development and progression of ACC will uncover new treatment strategies. A major hallmark of aging is the systemic accumulation of senescent cells. While senescent cells have been implicated in various age-related diseases, including cancer, their role in ACC remains poorly understood. ACC tumors from older patients have an enrichment of senescence-associated gene signatures. Moreover, advanced ACC patients are treated with etoposide, doxorubicin, and cisplatin (EDP), which are chemotherapies that induce senescence. While EDP offers short-term benefit in some patients, more than half will progress within 6-months. We hypothesize that the accumulation of senescent cells that arise after EDP treatment are ultimately tumor-supportive long-term. As a result, we postulate that the use of senolytic compounds that clear away senescent cells after EDP treatment will lead to improved survival outcomes for ACC patients. We developed a new ACC mouse model that provides a window to study the role of senescence in ACC tumor progression and treatment. Our model is based on adrenal specific loss of ZNRF3, which is a Wnt inhibitor that is frequently inactivated in human ACC tumors. Despite early adrenal hyperplasia, we showed that Znrf3 conditional knockout (cKO) mice do not develop adrenal tumors until 18-months of age, which corresponds to the peak age incidence in humans. Additionally, the adrenals of Znrf3 cKO mice show a robust senescence activation phenotype that precedes adrenal tumorigenesis. We hypothesize that the accumulation of senescent cells is pro-tumorigenic long-term. To test our hypothesis, we combined Znrf3 cKO mice with a newly established mouse model that enables selective ablation of senescent cells (ZKO-FDR mice). Ongoing aging studies will determine whether the removal of early and late senescent cells in ZKO-FDR mice reduces adrenal tumorigenesis. Further, we established new primary tumor cell lines from aged ZKO-FDR mice. These cell lines will facilitate testing of the pro-tumor mechanisms of senescence. Additionally, they will permit the removal of senescent cells, both genetically and pharmacologically with senolytics, as a new treatment strategy in ACC. Overall, this project aims to investigate the pro-tumor biology of age- and therapy-induced senescence in ACC. Results from these studies will advance our understanding of senescence in cancer and aid in the development of new therapeutic strategies for ACC, including senolytics. Presentation: 6/2/2024

Right ventricular function in mitral stenosis: plays a fundamental role.

The importance of the right ventricle (RV) was neglected or forgotten for decades. The RV has an essential function in cardiovascular physiology and pathology. The RV dysfunction is one of the causes of morbidity and mortality in valvular heart disease (VHD), especially in mitral stenosis (MS). Right ventricular systolic and diastolic function are important for the determination of clinical symptoms, exercise functional capacity, pre-procedure survival, and post-procedure outcome in patients with MS. Right ventricular dysfunction in MS with a sign of systemic venous congestion is easy to recognize, but MS without clinical evidence of RV dysfunction has not been studied. Detecting RV dysfunction earlier in MS is important in clinical practice.

Sequencing of Immunotherapy and Outcomes in Operable Clinical Stage III Melanoma: A National Cohort Study.

The impact of neoadjuvant immunotherapy (NIT) on overall survival (OS) in patients with resectable stage III melanoma remains unknown. We sought to identify factors associated with receipt of NIT and survival outcomes in patients with clinical stage III melanoma undergoing surgery. The National Cancer Database (2016-2020) was used to identify patients with clinical stage III melanoma who underwent surgery and received either NIT or adjuvant immunotherapy (AIT) only. Multivariable regression, Kaplan-Meier, and Cox proportional hazard methods were used to analyze variables of interest. Patients with clinical N3 disease had 2.5 times the odds of NIT compared to those with N1 disease (95% CI 1.74-3.49). There was no difference in 3-year OS between the two cohorts: 79% (95% CI 73%-85%) for NIT patients and 75% (95% CI 73%-76%) for AIT patients (p = 0.078). Patients with N2/N3 disease had improved 3-year OS of 79% with NIT versus 71% for AIT-only (HR 0.61, 95% CI 0.38-0.97, p = 0.037). NIT is given more selectively to clinical stage III patients with more advanced N category disease. Despite significant differences in N category between groups, there was no difference in OS observed at 3 years, and NIT was associated with a survival advantage among N2/N3 patients.

Identification of Disulfidptosis-Related LncRNA Subtypes, Establishment of a Prognostic Signature, and Characterization of Immune Infiltration in Ovarian Cancer.

Ovarian Cancer (OC) is a lethal malignant tumor with a poor prognosis. Disulfidptosis is a newly identified form of cell death caused by disulfide stress. Targeting disulfidptosis is a new metabolic therapeutic strategy in cancer treatment. We aimed to establish a disulfidptosis- related lncRNA signature for prognosis prediction and explore its treatment values in OC patients. Data from the TCGA and GTEx databases and a disulfidptosis gene set were used to establish a disulfidptosis-related lncRNA signature for prognosis prediction in OC patients. Then, we internally and externally (PCR) validated our model. We also built a nomogram to improve our model's predictive power. Afterward, GSEA was employed to explore our model's potential functions. The ESTIMATE, CIBERSORT, TIMER, and ssGSEA were applied to estimate the immune landscape. Finally, the drug sensitivity of certain drugs for OC patients was analyzed. We built a prognosis model based on seven drlncRNAs, including AL157871.2, HCP5, AC027348.1, AL109615.3, AL928654.1, LINC02585, and AC011445.1. Our model performed well by internal validation. PCR data also confirmed the same trend in the lncRNA levels. Furthermore, the nomogram-integrated age, grade, stage, and risk score could accurately predict the survival outcomes of OC patients. Subsequently, GSEA unveiled that our model genes enriched the Hedgehog signaling pathway, a key regulator in OC tumorigenesis. Our predictive signature was associated with immune checkpoints, such as PD-1(P < 0.01), PD-L1(P < 0.001), and CTLA4 (P < 0.01), which might help screen out OC patients who are sensitive to immunotherapy. Small molecule drugs, such as AZD-2281, GDC-0449, imatinib, and nilotinib, might benefit OC patients with different risk scores. Our disulfidptosis-related lncRNA signature comprised of AL157871.2, HCP5, AC027348.1, AL109615.3, AL928654.1, LINC02585, and AC011445.1 could serve as a prognostic biomarker and guidance to therapy response for OC patients.